chr1-203684896-G-T

Variant names:

• chr1-203684896-G-T
• rs10900585
• NM_001684.5:c.193+1498G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001684.5(ATP2B4):​c.193+1498G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,068 control chromosomes in the GnomAD database, including 52,086 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (52086 hom., cov: 32)
• Consequence: ATP2B4 NM_001684.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 30 publications found

Genes affected

ATP2B4 (HGNC:817): (ATPase plasma membrane Ca2+ transporting 4) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B4	NM_001684.5	c.193+1498G>T		intron_variant	Intron 2 of 20	ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3	c.193+1498G>T		intron_variant	Intron 2 of 21		NP_001001396.1
ATP2B4	NM_001365783.2	c.193+1498G>T		intron_variant	Intron 2 of 20		NP_001352712.1
ATP2B4	NM_001365784.2	c.193+1498G>T		intron_variant	Intron 2 of 20		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B4	ENST00000357681.10	c.193+1498G>T		intron_variant	Intron 2 of 20	1	NM_001684.5	ENSP00000350310.5
ATP2B4	ENST00000341360.7	c.193+1498G>T		intron_variant	Intron 2 of 21	1		ENSP00000340930.2
ATP2B4	ENST00000705901.1	c.193+1498G>T		intron_variant	Intron 2 of 20			ENSP00000516177.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124628 AN: 151950 Hom.: 52080 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.851

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.820 AC: 124668 AN: 152068 Hom.: 52086 Cov.: 32 AF XY: 0.819 AC XY: 60875 AN XY: 74310

African (AFR) AF: 0.646 AC: 26755 AN: 41426

American (AMR) AF: 0.894 AC: 13680 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3050 AN: 3472

East Asian (EAS) AF: 0.968 AC: 5004 AN: 5170

South Asian (SAS) AF: 0.846 AC: 4083 AN: 4824

European-Finnish (FIN) AF: 0.822 AC: 8673 AN: 10556

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60497 AN: 67994

Other (OTH) AF: 0.852 AC: 1801 AN: 2114

Alfa AF: 0.491 Hom.: 6704

Bravo AF: 0.820

Asia WGS AF: 0.907 AC: 3154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10900585; hg19: chr1-203654024;